Well, one obstacle is the fuel injection system is running in closed loop with the O2 sensor in the exhaust. If it gets a lot of air pumped at it, it'll think the engine is lean, and add fuel, probably to the limit of the calibration. Then, you'll have 4 really rich running cylinders, and 4 air pumps. You'd probably want to disable every other cylinder in the firing order, for smooth operation, so, if you built a dual exhuast system that contained the firing cylinders in one group, you could put the O2 sensor there, but that's a complicated mess. The speed density or mass air flow system, otherwise, should still be able to accurately (enough) meter fuel, even without knowing how many cylinders are working.
But, there's another issue. You'll still be wasting power by pumping air through the throttle and valves for 4 cylinders that aren't producing any power. If you were to disable the valves, then you wouldn't be - and the compression and expansion of the trapped air would roughly balance out (sure, there's heat transfer, but that's not my point, and it still probably balances out in the end). The *only* gain in your equation then is that the throttle is now slightly more open for the 4 cylinders that are producing work, thus reducing some of the throttling losses. I would imagine that the net gain would be negligable for the hassle.